Visible-Light-Mediated Cross Dehydrogenative Coupling of Thiols with Aldehydes: Metal-Free Synthesis of Thioesters at Room Temperature

Abstract

Thioesters play a crucial role in biological systems and serve as important building blocks for organic synthesis. Herein, Eosin Y and TBHP mediated photochemical cross dehydrogenative coupling (PCDC) between feedstock aldehydes and thiols has been described at room temperature to synthesize thioesters. This thioesterification protocol proceeds smoothly to give the desired products in good to excellent yields by the suitable PCDC of both alkyl/aryl- aldehydes with a variety of alkyl/aryl-thiols and generates water and t BuOH as green byproducts. This method is also found to be scalable with good efficiency. Mechanistic investigations reveal that under this photochemical condition, the formation of acyl radical can be achieved from aldehyde. This acyl radical was further intercepted with an intermediate disulfide, generated in situ via the dehydrogenation of thiol to give the desired thioester. Moreover, disulfides, which are relatively easier to handle, also provided good to excellent yields in the optimized reaction condition. This protocol was further extended toward the more challenging direct transformation of alcohols to thioesters.

Eosin Y mediated photo-catalytic C–H functionalization: C–C and C–S bond formation

“…Furthermore, during mechanistic studies, it has been revealed that the generation of an acyl radical from an aldehyde was intercepted by a disulfide intermediate to afford the desired thioester. 83…”

“…Furthermore, during mechanistic studies, it has been revealed that the generation of an acyl radical from an aldehyde was intercepted by a disulfide intermediate to afford the desired thioester. 83 Recently, Khade et al have reported the practical synthesis of 1,3-dithiolanes (182). These scaffolds were obtained without using any base and external additives from terminal aromatic and heteroaromatic alkynes (151) via the photoinduced catalyst eosin Y.…”

Synthetic Strategies for Versatile Thioester Building Blocks

“…The direct functionalization of sp 3 C−H bonds via radical chemistry constitutes an elegant platform for advanced organic synthesis [53] . Recently, α‐sp 3 C−H bonds of cyclic and acyclic ethers have been explored as synthetic handle for the incorporation of thioester functionality [54] .…”

A Recent Progress for the Synthesis of Thiocarboxylates

“…Roy [59] described the synthesis of thioesters at room temperature by eosin Y and tert ‐butyl hydroperoxide (TBHP) mediated photochemical cross dehydrogenation coupling. Various alkyl/aryl aldehydes or alcohols could give desirable products with thiols and produced water and butanol as green by‐products (Scheme 27).…”